tbuckley/cabot-search huggingface dataset:
Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial
Authors: Li Xuan, Yu Wang, Kaibo Yang, Ruoyang Shao, Fen Huang, Zhiping Fan, Peiru Chi, Yajing Xu, Na Xu, Lan Deng, Xudong Li, Xinquan Liang, Xiaodan Luo, Pengcheng Shi, Hui Liu, Zhixiang Wang, Ling Jiang, Ren Lin, Yan Chen, Sanfang Tu, Yu Zhang, Jing Sun, Xiaojun Huang, Qifa Liu
Journal: The Lancet Haematology (2023)
Optimal Care for Kidney Health: Development of a Merit-based Incentive Payment System (MIPS) Value Pathway
Authors: Sri Lekha Tummalapalli, Sarah A. Struthers, David L. White, Amy Beckrich, Yasmin Brahmbhatt, Kevin F. Erickson, Pranav S. Garimella, Edward R. Gould, Nupur Gupta, Krista L. Lentine, Susie Q. Lew, Frank Liu, Sumit Mohan, Michael Somers, Daniel E. Weiner, Scott D. Bieber, Mallika L. Mendu
Journal: Journal of the American Society of Nephrology (2023)

The Merit-based Incentive Payment System (MIPS) is a mandatory pay-for-performance program through the Centers for Medicare &amp; Medicaid Services (CMS) that aims to incentivize high-quality care, promote continuous improvement, facilitate electronic exchange of information, and lower health care costs. Previous research has highlighted several limitations of the MIPS program in assessing nephrology care delivery, including administrative complexity, limited relevance to nephrology care, and inability to compare performance across nephrology practices, emphasizing the need for a more valid and meaningful quality assessment program. This article details the iterative consensus-building process used by the American Society of Nephrology Quality Committee from May 2020 to July 2022 to develop the Optimal Care for Kidney Health MIPS Value Pathway (MVP). Two rounds of ranked-choice voting among Quality Committee members were used to select among nine quality metrics, 43 improvement activities, and three cost measures considered for inclusion in the MVP. Measure selection was iteratively refined in collaboration with the CMS MVP Development Team, and new MIPS measures were submitted through CMS's Measures Under Consideration process. The Optimal Care for Kidney Health MVP was published in the 2023 Medicare Physician Fee Schedule Final Rule and includes measures related to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use, hypertension control, readmissions, acute kidney injury requiring dialysis, and advance care planning. The nephrology MVP aims to streamline measure selection in MIPS and serves as a case study of collaborative policymaking between a subspecialty professional organization and national regulatory agencies.
Reversing the urgent and emergency care spiral of decline
Authors: Tim Cooksley, Mark Holland, Elizabeth Sapey
Journal: BMJ (2023)

NHS urgent and emergency care is under intolerable strain.This strain is increasingly causing harm to patients. 1 Timely and high quality patient care is often not being delivered due to overcrowding driven by workforce and capacity constraints. 2 3While the covid-19 pandemic has accentuated and arguably expedited the crisis; the spiral of decline in urgent and emergency care has been decades long and unless urgent action is taken, we may not yet have reached its nadir.
Rationally Designed Enzyme‐Resistant Peptidic Assemblies for Plasma Membrane Targeting in Cancer Treatment
Authors: Shijin Zhang, Xuewen Gong, Qinchuan Wei, Jiarong Lv, Enming Du, Jiaqing Wang, Wei Ji, Ji‐Liang Li
Journal: Advanced Healthcare Materials (2023)

Abstract Peptides are being increasingly important for subcellular targeted cancer treatment to improve specificity and reverse multidrug resistance. However, there has been yet any report on targeting plasma membrane (PM) through self‐assembling peptides. A simple synthetic peptidic molecule (tF4) is developed. It is revealed that tF4 is carboxyl esterase‐resistant and self‐assembles into vesical nanostructures. Importantly, tF4 assemblies interact with PM through orthogonal hydrogen bonding and hydrophobic interaction to regulate cancer cellular functions. Mechanistically, tF4 assemblies induce stress fiber formation, cytoskeleton reconstruction, and death receptor 4/5 (DR4/5) expression in cancer cells. DR4/5 triggers extrinsic caspase‐8 signaling cascade, resulting in cell death. The results provide a new strategy for developing enzyme‐resistant and PM‐targeting peptidic molecules against cancer.
Inequalities in the career pathway for paediatric HSCT and cellular therapy physicians
Authors: Carmelo Gurnari, Manuela Spadea, Rafaella Muratori, Valentine Jimenez, Vera Radici, Sheila Torrado, Nihar Desai, Julio Ropero, Ibrahim N Muhsen, Azada Ibrahimova, Justin Du Toit, Candice Laverne Hendricks, Nico Gagelmann, Claire Horgan
Journal: The Lancet Haematology (2023)
Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial
Authors: Stephen P Hunger, Thai Hoa Tran, Vaskar Saha, Meenakshi Devidas, Maria Grazia Valsecchi, Julie M Gastier-Foster, Giovanni Cazzaniga, Shalini C Reshmi, Michael J Borowitz, Anthony V Moorman, Nyla A Heerema, Andrew J Carroll, Patricia Martin-Regueira, Mignon L Loh, Elizabeth A Raetz, Kirk R Schultz, William B Slayton, Gunnar Cario, Martin Schrappe, Lewis B Silverman, Andrea Biondi
Journal: The Lancet Haematology (2023)
γ-Secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial
Authors: Andrew J Cowan, Margot J Pont, Blythe D Sather, Cameron J Turtle, Brian G Till, Edward N Libby, David G Coffey, Sherilyn A Tuazon, Brent Wood, Ted Gooley, Vicky Q Wu, Jenna Voutsinas, Xiaoling Song, Mazyar Shadman, Jordan Gauthier, Aude G Chapuis, Filippo Milano, David G Maloney, Stanley R Riddell, Damian J Green
Journal: The Lancet Oncology (2023)
Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies
Authors: Ernesto Lopez, Rajesh Karattil, Francesco Nannini, Gordon Weng-Kit Cheung, Lilian Denzler, Felipe Galvez-Cancino, Sergio Quezada, Martin A Pule
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Chimeric antigen receptor (CAR) T cells have shown remarkable results against B-cell malignancies, but only a minority of patients have long-term remission. The metabolic requirements of both tumor cells and activated T cells result in production of lactate. The export of lactate is facilitated by expression of monocarboxylate transporter (MCTs). CAR T cells express high levels of MCT-1 and MCT-4 on activation, while certain tumors predominantly express MCT-1. Methods Here, we studied the combination of CD19-specific CAR T-cell therapy with pharmacological blockade of MCT-1 against B-cell lymphoma. Results MCT-1 inhibition with small molecules AZD3965 or AR-C155858 induced CAR T-cell metabolic rewiring but their effector function and phenotype remained unchanged, suggesting CAR T cells are insensitive to MCT-1 inhibition. Moreover, improved cytotoxicity in vitro and antitumoral control on mouse models was found with the combination of CAR T cells and MCT-1 blockade. Conclusion This work highlights the potential of selective targeting of lactate metabolism via MCT-1 in combination with CAR T cells therapies against B-cell malignancies.
G4access identifies G-quadruplexes and their associations with open chromatin and imprinting control regions
Authors: Cyril Esnault, Talha Magat, Amal Zine El Aabidine, Encar Garcia-Oliver, Anne Cucchiarini, Soumya Bouchouika, David Lleres, Lutz Goerke, Yu Luo, Daniela Verga, Laurent Lacroix, Robert Feil, Salvatore Spicuglia, Jean-Louis Mergny, Jean-Christophe Andrau
Journal: Nature Genetics (2023)
The NSP4 T492I mutation increases SARS-CoV-2 infectivity by altering non-structural protein cleavage
Authors: Xiaoyuan Lin, Zhou Sha, Jakob Trimpert, Dusan Kunec, Chen Jiang, Yan Xiong, Binbin Xu, Zhenglin Zhu, Weiwei Xue, Haibo Wu
Journal: Cell Host & Microbe (2023)
Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer’s disease
Authors: Shan P. Yu, Michael Q. Jiang, Seong S. Shim, Soheila Pourkhodadad, Ling Wei
Journal: Molecular Neurodegeneration (2023)

Abstract Stroke and late-onset Alzheimer’s disease (AD) are risk factors for each other; the comorbidity of these brain disorders in aging individuals represents a significant challenge in basic research and clinical practice. The similarities and differences between stroke and AD in terms of pathogenesis and pathophysiology, however, have rarely been comparably reviewed. Here, we discuss the research background and recent progresses that are important and informative for the comorbidity of stroke and late-onset AD and related dementia (ADRD). Glutamatergic NMDA receptor (NMDAR) activity and NMDAR-mediated Ca 2+ influx are essential for neuronal function and cell survival. An ischemic insult, however, can cause rapid increases in glutamate concentration and excessive activation of NMDARs, leading to swift Ca 2+ overload in neuronal cells and acute excitotoxicity within hours and days. On the other hand, mild upregulation of NMDAR activity, commonly seen in AD animal models and patients, is not immediately cytotoxic. Sustained NMDAR hyperactivity and Ca 2+ dysregulation lasting from months to years, nevertheless, can be pathogenic for slowly evolving events, i.e. degenerative excitotoxicity, in the development of AD/ADRD. Specifically, Ca 2+ influx mediated by extrasynaptic NMDARs (eNMDARs) and a downstream pathway mediated by transient receptor potential cation channel subfamily M member (TRPM) are primarily responsible for excitotoxicity. On the other hand, the NMDAR subunit GluN3A plays a “gatekeeper” role in NMDAR activity and a neuroprotective role against both acute and chronic excitotoxicity. Thus, ischemic stroke and AD share an NMDAR- and Ca 2+ -mediated pathogenic mechanism that provides a common receptor target for preventive and possibly disease-modifying therapies. Memantine (MEM) preferentially blocks eNMDARs and was approved by the Federal Drug Administration (FDA) for symptomatic treatment of moderate-to-severe AD with variable efficacy. According to the pathogenic role of eNMDARs, it is conceivable that MEM and other eNMDAR antagonists should be administered much earlier, preferably during the presymptomatic phases of AD/ADRD. This anti-AD treatment could simultaneously serve as a preconditioning strategy against stroke that attacks ≥ 50% of AD patients. Future research on the regulation of NMDARs, enduring control of eNMDARs, Ca 2+ homeostasis, and downstream events will provide a promising opportunity to understand and treat the comorbidity of AD/ADRD and stroke.
Author Correction: Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial
Authors: Ingo K. Mellinghoff, Min Lu, Patrick Y. Wen, Jennie W. Taylor, Elizabeth A. Maher, Isabel Arrillaga-Romany, Katherine B. Peters, Benjamin M. Ellingson, Marc K. Rosenblum, Saewon Chun, Kha Le, Ania Tassinari, Sung Choe, Youssef Toubouti, Steven Schoenfeld, Shuchi S. Pandya, Islam Hassan, Lori Steelman, Jennifer L. Clarke, Timothy F. Cloughesy
Journal: Nature Medicine (2023)
Centering patients with advanced cancer includes supporting their caregivers
Authors: Erin E Kent
Journal: JNCI Journal of the National Cancer Institute (2023)

A diagnosis of advanced cancer ripples outward from patients, hitting their caregivers: partners, family members, and friends who step in to provide support.The social network around the patient absorbs the impact of cancer.Effects from both cancer and its treatment create a need for support that the health-care delivery system is unequipped to handle without the support of caregivers.Fortunately, increased attention to patientcenteredness has illuminated just how impactful cancer can be for caregivers.Unfortunately, the health-care system is not routinely set up to recognize, assess, or support caregivers.A resultant surge in supportive care interventions to improve quality of life in caregivers demonstrates the willingness of enterprising behavioral scientists to address this systemic gap.Understanding the state of the science of interventions for cancer caregivers, particularly of patients with the most severe disease, is needed to guide future iterations of this work.In this issue of the Journal, Chow and colleagues (1) provide a systematic review and meta-analysis of interventions to improve health outcomes among caregivers of patients with advanced cancer.The review focused on trials that delivered psychoeducational content, skills training, counseling, or team-based interventions with peer support and/or coping skills content.Interventions included those that could be administered to caregivers only, the patient-caregiver dyad, or the whole family.The authors closely adhered to systematic review best practices in accordance with Cochrane and Preferred Reporting Items for Systematic Review and Meta-Analyses (2,3).Out of over 12 000 identified references, 56 articles covering 49 unique trials were identified and reviewed.Interventions were primarily targeted at patient-caregiver dyads (39%), but 33% targeted caregivers and 29% targeted patients and their whole families.Most of the studies (69%) were conducted with caregivers of patients with mixed cancer types.Pooled intervention effects were estimated 1-3 months post intervention.For mental health outcomes, the pooled effects yielded standardized mean differences of 0.24 on caregiver quality of life, 0.14 on mental well-being, 0.27 on anxiety, and 0.34 on depression compared with standard care (attentional or active controls).On the contrary, the metaanalysis suggested very small effects of the interventions examined on physical well-being.The intervention effects on quality of life and mental health included in the meta-analysis are promising, particularly given the high prevalence of depression and
Author Correction: Pre-eclampsia
Authors: Evdokia Dimitriadis, Daniel L. Rolnik, Wei Zhou, Guadalupe Estrada-Gutierrez, Kaori Koga, Rossana P. V. Francisco, Clare Whitehead, Jon Hyett, Fabricio da Silva Costa, Kypros Nicolaides, Ellen Menkhorst
Journal: Nature Reviews Disease Primers (2023)
Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin
Authors: Benjamin Voisin, Vinod Nadella, Thomas Doebel, Shubham Goel, Keiko Sakamoto, Otgonzaya Ayush, Jay-Hyun Jo, Michael C. Kelly, Tetsuro Kobayashi, Jean X. Jiang, Ying Hu, Chunhua Yan, Keisuke Nagao
Journal: Immunity (2023)
Hepatic soluble epoxide hydrolase activity regulates cerebral Aβ metabolism and the pathogenesis of Alzheimer’s disease in mice
Authors: Yu Wu, Jing-Hua Dong, Yong-Feng Dai, Min-Zhen Zhu, Meng-Yao Wang, Yuan Zhang, Yi-Da Pan, Xin-Rui Yuan, Zhi-Xin Guo, Chen-Xi Wang, Yuan-Qing Li, Xin-Hong Zhu
Journal: Neuron (2023)
m6A RNA modification regulates innate lymphoid cell responses in a lineage-specific manner
Authors: Yingyu Zhang, Wanwei Zhang, Jingyao Zhao, Takamasa Ito, Jiacheng Jin, Alexis O. Aparicio, Junsong Zhou, Vincent Guichard, Yinshan Fang, Jianwen Que, Joseph F. Urban, Jacob H. Hanna, Sankar Ghosh, Xuebing Wu, Lei Ding, Uttiya Basu, Yuefeng Huang
Journal: Nature Immunology (2023)
Spatial mapping of cellular senescence: emerging challenges and opportunities
Authors: Aditi U. Gurkar, Akos A. Gerencser, Ana L. Mora, Andrew C. Nelson, Anru R. Zhang, Anthony B. Lagnado, Archibald Enninful, Christopher Benz, David Furman, Delphine Beaulieu, Diana Jurk, Elizabeth L. Thompson, Fei Wu, Fernanda Rodriguez, Grant Barthel, Hao Chen, Hemali Phatnani, Indra Heckenbach, Jeffrey H. Chuang, Jeremy Horrell, Joana Petrescu, Jonathan K. Alder, Jun Hee Lee, Laura J. Niedernhofer, Manoj Kumar, Melanie Königshoff, Marta Bueno, Miiko Sokka, Morten Scheibye-Knudsen, Nicola Neretti, Oliver Eickelberg, Peter D. Adams, Qianjiang Hu, Quan Zhu, Rebecca A. Porritt, Runze Dong, Samuel Peters, Stella Victorelli, Thomas Pengo, Timur Khaliullin, Vidyani Suryadevara, Xiaonan Fu, Ziv Bar-Joseph, Zhicheng Ji, João F. Passos
Journal: Nature Aging (2023)
Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors
Authors: Spencer E. Brightman, Angelica Becker, Rukman R. Thota, Martin S. Naradikian, Leila Chihab, Karla Soria Zavala, Ashmitaa Logandha Ramamoorthy Premlal, Ryan Q. Griswold, Joseph S. Dolina, Ezra E. W. Cohen, Aaron M. Miller, Bjoern Peters, Stephen P. Schoenberger
Journal: Nature Immunology (2023)

CD4
CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results
Authors: Jae H. Park, Karthik Nath, Sean M. Devlin, Craig S. Sauter, M. Lia Palomba, Gunjan Shah, Parastoo Dahi, Richard J. Lin, Michael Scordo, Miguel-Angel Perales, Roni Shouval, Ana Alarcon Tomas, Elizabeth Cathcart, Elena Mead, Bianca Santomasso, Andrei Holodny, Renier J. Brentjens, Isabelle Riviere, Michel Sadelain
Journal: Nature Medicine (2023)
Potent and uniform fetal hemoglobin induction via base editing
Authors: Thiyagaraj Mayuranathan, Gregory A. Newby, Ruopeng Feng, Yu Yao, Kalin D. Mayberry, Cicera R. Lazzarotto, Yichao Li, Rachel M. Levine, Nikitha Nimmagadda, Erin Dempsey, Guolian Kang, Shaina N. Porter, Phillip A. Doerfler, Jingjing Zhang, Yoonjeong Jang, Jingjing Chen, Henry W. Bell, Merlin Crossley, Senthil Velan Bhoopalan, Akshay Sharma, John F. Tisdale, Shondra M. Pruett-Miller, Yong Cheng, Shengdar Q. Tsai, David R. Liu, Mitchell J. Weiss, Jonathan S. Yen
Journal: Nature Genetics (2023)
Simultaneous quantitative imaging of two PET radiotracers via the detection of positron–electron annihilation and prompt gamma emissions
Authors: Edwin C. Pratt, Alejandro Lopez-Montes, Alessia Volpe, Michael J. Crowley, Lukas M. Carter, Vivek Mittal, Nagavarakishore Pillarsetty, Vladimir Ponomarev, Jose M. Udías, Jan Grimm, Joaquin L. Herraiz
Journal: Nature Biomedical Engineering (2023)
Longevity factor klotho enhances cognition in aged nonhuman primates
Authors: Stacy A. Castner, Shweta Gupta, Dan Wang, Arturo J. Moreno, Cana Park, Chen Chen, Yan Poon, Aaron Groen, Kenneth Greenberg, Nathaniel David, Tom Boone, Mark G. Baxter, Graham V. Williams, Dena B. Dubal
Journal: Nature Aging (2023)

Abstract Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.
Changes in mid‐regional pro‐adrenomedullin during treatment with sacubitril/valsartan
Authors: Peder L. Myhre, Yuxi Liu, Ian J. Kulac, Brian L. Claggett, Margaret F. Prescott, G. Michael Felker, Javed Butler, Ileana L. Piña, Jean L. Rouleau, Michael R. Zile, John J.V. McMurray, Jonathan H. Ward, Scott D. Solomon, James L. Januzzi
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment. Methods and results Mid‐regional pro‐adrenomedullin (MR‐proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort. Median (Q1–Q3) baseline MR‐proADM concentrations were 0.80 (0.59–0.99) nmol/L in HFrEF and 0.88 (0.68–1.20) nmol/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR‐proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan‐treated patients (median 2%). Greater increases in MR‐proADM were associated with higher Sac/Val doses. Changes in MR‐proADM correlated weakly with changes in N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR‐proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status. Conclusions MR‐proAD concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR‐proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure. Clinical Trial Registration: PROVE‐HF ClinicalTrials.gov Identifier: NCT02887183, PARAMOUNT ClinicalTrials.gov Identifier: NCT00887588.
A scoping review of heart failure transitional care quality indicators and outcomes for use in clinical care and research
Authors: Suzanne Oskouie, Faith Michael, Sera Whitelaw, Biykem Bozkurt, Gregg C. Fonarow, Harriette G.C. Van Spall
Journal: European Journal of Heart Failure (2023)

Aims There are no accepted quality indicators for transitional care following hospitalization for heart failure (HF). Current quality measures focus on 30‐day readmissions without accounting for competing risks such as death. In this scoping review of clinical trials, we aimed to develop a set of HF transitional care quality indicators for clinical or research applications following hospitalization for HF. Methods and results We performed a scoping review using MEDLINE, Embase, CINAHL, HealthSTAR, reference lists and grey literature from January 1990 to November 2022. We included randomized controlled trials (RCTs) of adults hospitalized for HF who received a healthcare service or strategy intervention that aimed to improve patient‐reported or clinical outcomes. We independently extracted data and performed a qualitative synthesis of the results. We generated a list of process, structure, patient‐reported, and clinical measures that could be used as quality indicators. We highlighted process indicators that were associated with improved clinical outcomes and patient‐reported outcomes that had high adherence to COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) and United States Food and Drug Administration standards. From 42 RCTs included in the study, we identified a set of process, structure, patient‐reported, and clinical indicators that could be used as transitional care measures in clinical or research settings. Conclusion In this scoping review, we developed a list of quality indicators that could guide clinical efforts or serve as research endpoints in transitional care in HF. Clinicians, researchers, institutions, and policymakers can use the indicators to guide management, design research, allocate resources, and fund services that improve clinical outcomes.
Tackling rare conditions: the consultant dermatologist
Authors: Kathy Oxtoby
Journal: BMJ (2023)

Edel O'Toole's love of dermatology comes from a desire to help all patients with any skin condition-no matter how rare."Recently an older patient presented with a rare disorder-he had had pain in his feet his whole life.I prescribed the drug erlotinib and his pain went away within 24 hours, which was miraculous," she says.